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| Expressionsanalyse des Killer-Inhibitory-Rezeptors CD158b auf CD8 T-Lymphozyten, die spezifisch für Humanes Cytomegalievirus sind Frömmel, Claudia Bettina |
| Main title | Expressionsanalyse des Killer-Inhibitory-Rezeptors CD158b auf CD8 T-Lymphozyten, die spezifisch für Humanes Cytomegalievirus sind |
| Title variations | Analysis of the Expression of Killer Inhibitory Receptor CD158b on CD8 T-Lymphocytes specific for human Cytomegalovirus |
| Author(s) | Frömmel, Claudia Bettina
Place of birth: Berlin, Deutschland |
| 1. Referee | Priv.-Doz. Dr. med. F. Kern |
| Further Referee(s) | Prof. Dr. M. Scholz Prof. Dr. med. vet. W. Hammerschmidt |
| Keywords | Killer Inhibitory Receptors, CD158b, CD8 T-Lymphocytes, Cytomegalovirus |
| Classification (DDC) | 610 Medical sciences; Medicine |
| Summary | HCMV-specific CD8 T-lymphocytes play an important role in control of viral replication and preventing HCMV disease. Direct assessment of virus specific cells by peptide specific short-time stimulation assay and subsequent measurement of intracellular cytokine production as well as direct visualization by HCMV-peptide-MHC-tetrameric complexes allow phenotypic characterization of different T-cell subsets. Expression of CD158b on human CD8 T-cells is associated with terminal effector differentiation typically reflected by expression of CD57, CD45RO and down-regulation or lack of CD27, CD28, L-Selectin, and CCR7. It has been proposed that Killer Inhibitory Receptor positive T-cells occur in response to chronic antigen-driven stimulation by reactivated endogenous pathogens, including different herpes viruses, such as HCMV, EBV as well as certain tumor antigens. If this were the case, one might expect that chronically stimulated HCMV specific CD8 T-cells should express KIR. This work addresses the distribution of HCMV specific CD8 T-cells in the CD158b-positive and -negative subsets using multi-color flow-cytometry, cell sorting and a semi-quantitative clonotype PCR. It shows that for the most part HCMV specific CD8 T-cells are not contained in the CD158b positive subset. In addition it was demonstrated that these cells produce clearly more IFN-g upon stimulation with Ionomycin and OKT3 compared to the negative subset, but the contrary is true after stimulation with SEB. While CD158b positive CD8 T-cells are likely to represent terminally differentiated T-cells, the distribution of this marker in skewed, and HCMV-specific T-cells are either underrepresented or absent in this subset. Examination of specific Vβ-families revealed in the CD158b positive population an oligoclonal distribution with expansion of certain Vβ-families. These observations are discussed considering aspects of methodology as an characteristic of the generation of memory T-cells. Therefore expression of CD158b is not simply a marker of antigen experienced CD8 T-lymphocytes. Its expression may represent different states of the development of memory T-cells. On the other hand HCMV may not be the specific antigen for the KIR-expressing T-cell subset in healthy subjects. In this context it may be interesting to investigate whether the expression of CD158b is different in healthy subjects and patients with HCMV disease or in the course of primary infection. |
| Documents |
FUDISS_derivate_000000002285
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| FU Department | Department of Medicine - Charité - University Medicine Berlin |
| Year of publication | 2006 |
| Document type | Doctoral thesis |
| Media type/Format | Text |
| Language | German |
| Terms of use/Rights | Nutzungsbedingungen |
| Date of defense | 2006-09-22 |
| Created at | 2006-08-23 : 12:00:00 |
| Last changed | 2010-02-19 : 11:44:40 |
| Old Darwin URL | http://www.diss.fu-berlin.de/2006/454/ |
| Static URL | http://www.diss.fu-berlin.de/diss/receive/FUDISS_thesis_000000002285 |
| NBN | urn:nbn:de:kobv:188-fudissthesis000000002285-3 |
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